The renal secretion of organic acids is major medical importance because of its usefulness in evaluating renal function and its role in the excretion of a variety of commonly used drugs. A primary step in this secretory process is the active transport of the compound into the tubular cell at its blood side. There results a selectively high local drug concentration in cells of the proximal tubule. Although many organic acids are not secreted as rapidly as is p-aminohippurate (PAH), certain of them may exhibit high renal cortical concentrations resulting from active transport. One such agent is iodipamide, and another is the commonly used antibiotic cephaloridine. Although not secreted into the urine, relative cortical cephaloridine concentrations in vivo are 7 to 8 times those of inulin. This uptake is strikingly inhibited by various organic acids, by dinitrophenol and by anoxia. Of further interest, cephaloridine is selectively toxic to proximal renal tubule cells, and this toxicity can be prevented by a variety of organic anions. Studies have been designed to test the hypothesis that cephaloridine is actively transported into the proximal tubule cell, but that little or no secretion occurs because of its inability to move from the cell into the tubular urine. Further studies will examine the interaction of the commonly used diuretic furosemide, which can both inhibit cortical cephaloridine uptake and protect against its nephrotoxicity. Finally, the transport and toxicity of other cephalosporins will be studied for the purpose of further evaluating the relationship between cell uptake and toxicity of the cephalosporins in general. It is expected that the proposed studies will contribute significantly to the general understanding of renal pharmacology and add new techniques for the study of renal transport.